Telomerase promoter mutations in cancer: an emerging molecular biomarker?

Authors and Affiliations:

João Vinagre^1,2,, Vasco Pinto^1,3,, Ricardo Celestino^1,4, Marta Reis¹, Helena Populo¹, Paula Boaventura¹, Miguel Melo^1,5,6, Telmo Catarino¹, Jorge Lima^1,3, José Manuel Lopes^1,3,7, Valdemar Máximo^1,3, Manuel Sobrinho-Simões^1,3,7 e Paula Soares^1,3.

¹Instituto de Patologia e Imunologia Molecular da Universidade do Porto

²Instituto de Ciências Biomédicas Abel Salazar da Universidade do Porto

³Faculdade de Medicina da Universidade do Porto

⁴Escola Superior de Tecnologia da Saúde do Porto (IPP)

⁵Departamento de Endocrinologia, Diabetes e Metabolismo da Universidade e Hospital Centro de Coimbra

⁶Unidade de Endocrinologia, Faculdade de Medicina da Universidade de Coimbra

⁷Serviço de Anatomia Patológica do Centro Hospitalar São João, Porto

Abstract:

Cell immortalization has been considered for a long time as a classic hallmark of cancer cells. Besides telomere maintenance due to the “alternative mechanism of telomere lengthening” (ALT) it was advanced that such immortalization could be due to telomerase reactivation but the mechanisms underlying such reactivation remained elusive.

Mutations in the coding region of telomerase gene are very rare in the cancer setting, despite being associated with some degenerative diseases. Recently, mutations in telomerase (TERT) gene promoter were found in sporadic and familial melanoma and subsequently in several cancer models, notably in gliomas, thyroid cancer and bladder cancer.  The importance of these findings has been reinforced by the association of TERT mutations in some cancer types with tumour aggressiveness and patient survival. In the first part of this review we summarize the data on the biology of telomeres and telomerase, available methodological approaches and non-neoplastic diseases associated with telomere dysfunction.  In the second part, we review the information on telomerase expression and genetic alterations in the most relevant types of cancer (skin, thyroid, bladder and central nervous system) on record, and discuss the value of telomerase as a new biomarker with impact on the prognosis and survival of the patients and as a putative therapeutic target.

Journal: Virchows Archiv, 2014

Link: http://link.springer.com/article/10.1007%2Fs00428-014-1608-4